Improving Patients’ Experience and Outcome of Total Joint Replacement: the RESTORE Programme

BACKGROUND: Total hip replacements (THRs) and total knee replacements (TKRs) are common elective procedures. In the REsearch STudies into the ORthopaedic Experience (RESTORE) programme, we explored the care and experiences of patients with osteoarthritis after being listed for THR and TKR up to the time when an optimal outcome should be expected. OBJECTIVE: To undertake a programme of research studies to work towards improving patient outcomes after THR and TKR. METHODS: We used methodologies appropriate to research questions: systematic reviews, qualitative studies, randomised controlled trials (RCTs), feasibility studies, cohort studies and a survey. Research was supported by patient and public involvement. RESULTS: Systematic review of longitudinal studies showed that moderate to severe long-term pain affects about 7–23% of patients after THR and 10–34% after TKR. In our cohort study, 10% of patients with hip replacement and 30% with knee replacement showed no clinically or statistically significant functional improvement. In our review of pain assessment few research studies used measures to capture the incidence, character and impact of long-term pain. Qualitative studies highlighted the importance of support by health and social professionals for patients at different stages of the joint replacement pathway. Our review of longitudinal studies suggested that patients with poorer psychological health, physical function or pain before surgery had poorer long-term outcomes and may benefit from pre-surgical interventions. However, uptake of a pre-operative pain management intervention was low. Although evidence relating to patient outcomes was limited, comorbidities are common and may lead to an increased risk of adverse events, suggesting the possible value of optimising pre-operative management. The evidence base on clinical effectiveness of pre-surgical interventions, occupational therapy and physiotherapy-based rehabilitation relied on small RCTs but suggested short-term benefit. Our feasibility studies showed that definitive trials of occupational therapy before surgery and post-discharge group-based physiotherapy exercise are feasible and acceptable to patients. Randomised trial results and systematic review suggest that patients with THR should receive local anaesthetic infiltration for the management of long-term pain, but in patients receiving TKR it may not provide additional benefit to femoral nerve block. From a NHS and Personal Social Services perspective, local anaesthetic infiltration was a cost-effective treatment in primary THR. In qualitative interviews, patients and health-care professionals recognised the importance of participating in the RCTs. To support future interventions and their evaluation, we conducted a study comparing outcome measures and analysed the RCTs as cohort studies. Analyses highlighted the importance of different methods in treating and assessing hip and knee osteoarthritis. There was an inverse association between radiographic severity of osteoarthritis and pain and function in patients waiting for TKR but no association in THR. Different pain characteristics predicted long-term pain in THR and TKR. Outcomes after joint replacement should be assessed with a patient-reported outcome and a functional test. CONCLUSIONS: The RESTORE programme provides important information to guide the development of interventions to improve long-term outcomes for patients with osteoarthritis receiving THR and TKR. Issues relating to their evaluation and the assessment of patient outcomes are highlighted. Potential interventions at key times in the patient pathway were identified and deserve further study, ultimately in the context of a complex intervention.

Building peace by supporting post-conflict electoral processes

Les élections post-conflit ou élections de sortie de crise organisées sous l’égide de la communauté internationale en vue de rétablir la paix dans les pays sortant de violents conflits armés ont un bilan mixte caractérisé par le succès ou l’échec selon les cas. Ce bilan mitigé représente le problème principal auquel cette recherche tente de répondre à travers les questions suivantes : l’assistance électorale étrangère est-elle efficace comme outil de rétablissement de la paix dans les sociétés post-conflit? Qu’est ce qui détermine le succès ou l’échec des élections post-conflit à contribuer efficacement au rétablissement de la paix dans les sociétés déchirées par la guerre? Pour résoudre cette problématique, cette thèse développe une théorie de l’assistance électorale en période post-conflit centrée sur les parties prenantes à la fois du conflit armé et du processus électoral. Cette théorie affirme que l’élément clé pour le succès des élections post-conflit dans le rétablissement de la paix est le renforcement de la capacité de négociation des parties prenantes à la fois dans le processus de paix et dans le processus électoral post-conflit. Dans les situations post-conflit, une assistance électorale qui se voudrait complète et efficace devra combiner à la fois le processus électoral et le processus de paix. L’assistance électorale sera inefficace si elle se concentre uniquement sur les aspects techniques du processus électoral visant à garantir des élections libres, transparentes et équitables. Pour être efficace, l’accent devra également être mis sur les facteurs supplémentaires qui peuvent empêcher la récurrence de la guerre, tels que l’habilité des individus et des groupes à négocier et à faire des compromis sur les grandes questions qui peuvent menacer le processus de paix. De fait, même des élections transparentes comme celles de 1997 au Liberia saluées par la communauté internationale n’avaient pas réussi à établir des conditions suffisantes pour éviter la reprise des hostilités. C’est pourquoi, pour être efficace, l’assistance électorale dans les situations de post-conflit doit prendre une approche globale qui priorise l’éducation civique, la sensibilisation sur les droits et responsabilités des citoyens dans une société démocratique, le débat public sur les questions qui divisent, la participation politique, la formation au dialogue politique, et toute autre activité qui pourrait aider les différentes parties à renforcer leur capacité de négociation et de compromis. Une telle assistance électorale fera une contribution à la consolidation de la paix, même dans le contexte des élections imparfaites, comme celles qui se sont détenues en Sierra Leone en 2002 ou au Libéria en 2005. Bien que la littérature sur l’assistance électorale n’ignore guère l’importance des parties prenantes aux processus électoraux post-conflit (K. Kumar, 1998, 2005), elle a fortement mis l’accent sur les mécanismes institutionnels. En effet, la recherche académique et professionnelle est abondante sur la réforme des lois électorales, la reforme constitutionnelle, et le développement des administrations électorales tels que les commissions électorales, ainsi que l’observation électorale et autres mécanismes de prévention de la fraude électorale, etc. (Carothers & Gloppen, 2007). En d’autres termes, les décideurs et les chercheurs ont attribué jusqu’à présent plus d’importance à la conception et au fonctionnement du cadre institutionnel et des procédures électorales. Cette thèse affirme qu’il est désormais temps de prendre en compte les participants eux-mêmes au processus électoral à travers des types d’assistance électorale qui favoriseraient leur capacité à participer à un débat pacifique et à trouver des compromis aux questions litigieuses. Cette approche plus globale de l’assistance électorale qui replace l’élection post-conflit dans le contexte plus englobant du processus de paix a l’avantage de transformer le processus électoral non pas seulement en une expérience d’élection de dirigeants légitimes, mais aussi, et surtout, en un processus au cours duquel les participants apprennent à régler leurs points de vue contradictoires à travers le débat politique dans un cadre institutionnel avec des moyens légaux et légitimes. Car, si le cadre institutionnel électoral est important, il reste que le résultat du processus électoral dépendra essentiellement de la volonté des participants à se conformer au cadre institutionnel et aux règles électorales.

Developmental TVET rhetoric in-action: the White Paper for post-school education and training in South Africa

This paper explores the extent to which latest developments in the Technical and Vocational Education and Training System in South Africa respond to key principles espoused for a developmental, democratic and inclusionary ideal. The White Paper for post school education and training approved by Cabinet in November, 2013 is referred to by the Minister as the “definitive statement of the governments vision for the post school system” and as such represents a crucial strategy document intended to chart the TVET direction to 2030. Using key theoretical constructs from development theory, this paper provides an assessment of the TVET strategy contained is the paper and explores the extent to which it does respond to the agenda defined by the promise. It is argued that the challenges outlined are not yet able to provide the blueprint for a TVET transformative vision. It is concluded that while the development rhetoric contained in the paper is plausible, the creative tinkering of the system is unlikely to lead to the radical revisioning necessary for a truly transformative TVET system. The underlying assumptions regarding purpose, impact and outcome will need to be carefully reconsidered if the system is to be responsive to the promises of the democratic developmental ideal to which the government is committed. (DIPF/Orig.)

Effect of remote ischaemic preconditioning in cardiac dysfunction and end-organ injury following cardiac surgery with cardiopulmonary bypass in children: A translational approach investigating clinical outcome and myocardial molecular biology

Congenital heart disease (CHD) is the most common birth defect, causing an important rate of morbidity and mortality. Treatment of CHD requires surgical correction in a significant percentage of cases which exposes patients to cardiac and end organ injury. Cardiac surgical procedures often require the utilisation of cardiopulmonary bypass (CPB), a system that replaces heart and lungs function by diverting circulation into an external circuit. The use of CPB can initiate potent inflammatory responses, in addition a proportion of procedures require a period of aortic cross clamp during which the heart is rendered ischaemic and is exposed to injury. High O2 concentrations are used during cardiac procedures and when circulation is re-established to the heart which had adjusted metabolically to ischaemia, further injury is caused in a process known as ischaemic reperfusion injury (IRI). Several strategies are in place in order to protect the heart during surgery, however injury is still caused, having detrimental effects in patients at short and long term. Remote ischaemic preconditioning (RIPC) is a technique proposed as a potential cardioprotective measure. It consists of exposing a remote tissue bed to brief episodes of ischaemia prior to surgery in order to activate protective pathways that would act during CPB, ischaemia and reperfusion. This study aimed to assess RIPC in paediatric patients requiring CHD surgical correction with a translational approach, integrating clinical outcome, marker analysis, cardiac function parameters and molecular mechanisms within the cardiac tissue. A prospective, single blinded, randomized, controlled trial was conducted applying a RIPC protocol to randomised patients through episodes of limb ischaemia on the day before surgery which was repeated right before the surgery started, after anaesthesia induction. Blood samples were obtained before surgery and at three post-operative time points from venous lines, additional pre and post-bypass blood samples were obtained from the right atrium. Myocardial tissue was resected during the ischaemic period of surgery. Echocardiographic images were obtained before the surgery started after anaesthetic induction and the day after surgery, images were stored for later off line analysis. PICU surveillance data was collected including ventilation parameters, inotrope use, standard laboratory analysis and six hourly blood gas analysis. Pre and post-operative quantitation of markers in blood specimens included cardiac troponin I (cTnI) and B-type natriuretic peptide (BNP), inflammatory mediators including interleukins IL-6, IL-8, IL-10, tumour necrosis factor (TNF-α), and the adhesion molecules ICAM-1 and VCAM-1; the renal marker Cystatin C and the cardiovascular markers asymmetric dymethylarginine (ADMA) and symmetric dymethylarginine (SDMA). Nitric oxide (NO) metabolites and cyclic guanosine monophosphate (cGMP) were measured before and after bypass. Myocardial tissue was processed at baseline and after incubation at hyperoxic concentration during four hours in order to mimic surgical conditions. Expression of genes involved in IRI and RIPC pathways was analysed including heat shock proteins (HSPs), toll like receptors (TLRs), transcription factors nuclear factor κ-B (NF- κ-B) and hypoxia inducible factor 1 (HIF-1). The participation of hydrogen sulfide enzymatic genes, apelin and its receptor were explored. There was no significant difference according to group allocation in any of the echocardiographic parameters. There was a tendency for higher cTnI values and inotropic score in control patients post-operatively, however this was not statistically significant. BNP presented no significant difference according to group allocation. Inflammatory parameters tended to be higher in the control group, however only TNF- α was significantly higher. There was no difference in levels of Cystatin C, NO metabolites, cGMP, ADMA or SDMA. RIPC patients required shorter PICU stay, all other clinical and laboratory analysis presented no difference related to the intervention. Gene expression analysis revealed interesting patterns before and after incubation. HSP-60 presented a lower expression at baseline in tissue corresponding to RIPC patients, no other differences were found. This study provided with valuable descriptive information on previously known and newly explored parameters in the study population. Demographic characteristics and the presence of cyanosis before surgery influenced patterns of activity in several parameters, numerous indicators were linked to the degree of injury suffered by the myocardium. RIPC did not reduce markers of cardiac injury or improved echocardiographic parameters and it did not have an effect on end organ function; some effects were seen in inflammatory responses and gene expression analysis. Nevertheless, an important clinical outcome indicator, PICU length of stay was reduced suggesting benefit from the intervention. Larger studies with more statistical power could determine if the tendency of lower injury and inflammatory markers linked to RIPC is real. The present results mostly support findings of larger multicentre trials which have reported no cardiac benefit from RIPC in paediatric cardiac surgery.

Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke

Background Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens — aspirin plus extendedrelease dipyridamole (ASA–ERDP) versus clopidogrel. Methods In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. Results A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA–ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA–ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA–ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA–ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11). Conclusions The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA–ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. (ClinicalTrials.gov number, NCT00153062.)

Granulocyte-colony stimulating factor in experimental stroke and its effects on infarct size and functional outcome: a systematic review

Background Granulocyte-colony stimulating factor (G-CSF) shows promise as a treatment for stroke. This systematic review assesses G-CSF in experimental ischaemic stroke. Methods Relevant studies were identified with searches of Medline, Embase and PubMed. Data were extracted on stroke lesion size, neurological outcome and quality, and analysed using Cochrane Review Manager using random effects models; results are expressed as standardised mean difference (SMD) and odds ratio (OR). Results Data were included from 19 publications incorporating 666 animals. G-CSF reduced lesion size significantly in transient (SMD -1.63, p<0.00001) but not permanent (SMD -1.56, p=0.11) focal models of ischaemia. Lesion size was reduced at all doses and with treatment commenced within 4 hours of transient ischaemia. Neurological deficit (SMD -1.37, p=0.0004) and limb placement (SMD -1.88, p=0.003) improved with G-CSF; however, locomotor activity (>4 weeks post ischaemia) was not (SMD 0.76, p=0.35). Death (OR 0.27, p<0.0001) was reduced with G-CSF. Median study quality was 4 (range 0-7/8); Egger’s test suggested significant publication bias (p=0.001). Conclusions G-CSF significantly reduced lesion size in transient but not permanent models of ischaemic stroke. Motor impairment and death were also reduced. Further studies assessing dose-response, administration time, length of ischaemia and long-term functional recovery are needed.

THE TERMINATION PHASE: THERAPISTS’ PERSPECTIVE ON THE THERAPEUTIC RELATIONSHIP AND OUTCOME

The termination phase of treatment is recognized as a significant aspect of the therapy process and yet remains vastly understudied in psychotherapy literature. In the present study, therapists’ perspectives were used to examine how three elements of the therapy relationship (working alliance, real relationship and transference) during the termination phase relate to perceived client sensitivity to loss, termination phase evaluation and overall treatment outcome. Self-report data was gathered from 233 therapists, recruited from two Divisions of the American Psychological Association. Therapists completed measures for their work with a client with whom they could identify a termination phase of treatment. Results revealed that the working alliance and real relationship during the termination phase related positively to termination phase evaluation and overall treatment outcome, whereas negative transference during the termination phase related negatively to overall treatment outcome. Therapists’ perceptions of client sensitivity to loss related positively to both negative and positive transference during the termination phase. Post-hoc analyses revealed only the working alliance during the termination phase uniquely predicted overall treatment outcome in a model with the three therapy relationship elements examined together. On the other hand, all three therapy relationship variables during the termination phase uniquely predicted termination phase evaluation, when examined together. Limitations and implications of these findings are discussed, and recommendations for future study are suggested.

In situ epicatechin-loaded hydrogel implants for local drug delivery to spinal column for effective management of post-traumatic spinal injuries

Purpose: To prepare hydrogels loaded with epicatechin, a strong antioxidant, anti-inflammatory, and neuroprotective tea flavonoid, and characterise them in situ as a vehicle for prolonged and safer drug delivery in patients with post-traumatic spinal cord injury. Methods: Five in situ gel formulations were prepared using chitosan and evaluated in terms of their visual appearance, clarity, pH, viscosity, and in vitro drug release. In vivo anti-inflammatory activity was determined and compared with 2 % piroxicam gel as standard. Motor function activity in a rat model of spinal injury was examined comparatively with i.v. methylprednisolone as standard. Results: The N-methyl pyrrolidone solution (containing 1 % w/w epicatechin with 2 to 10 % w/w chitosan) of the in situ gel formulation had a uniform pH in the range of 4.01 ± 0.12 to 4.27 ± 0.02. High and uniform drug loading, ranging from 94.48 ± 1.28 to 98.08 ± 1.24 %, and good in vitro drug release (79.48 ± 2.84 to 96.48 ± 1.02 % after 7 days) were achieved. The in situ gel prepared from 1 % epicatechin and 2 % chitosan (E5) showed the greatest in vivo anti-inflammatory activity (60.58 % inhibition of paw oedema in standard carrageenan-induced hind rat paw oedema model, compared with 48.08 % for the standard). The gels showed significant therapeutic effectiveness against post-traumainduced spinal injury in rats. E5 elicited maximum motor activity (horizontal bar test) in the spinal injury rat model; the rats that received E5 treatment produced an activity score of 3.62 ± 0.02 at the end of 7 days, compared with 5.0 ± 0.20 following treatment with the standard. Conclusion: In situ epicatechin-loaded gel exhibits significant neuroprotective and anti-inflammatory effects, and therefore can potentially be used for prolonged and safe drug delivery in patients with traumatic spinal cord injury.

Post-CMOS compatible high-throughput fabrication of AIN-based piezoelectric microcantilevers

A post-complementary metal oxide semiconductor (CMOS) compatible microfabrication process of piezoelectric cantilevers has been developed. The fabrication process is suitable for standard silicon technology and provides low-cost and high-throughput manufacturing. This work reports design, fabrication and characterization of piezoelectric cantilevers based on aluminum nitride (AlN) thin films synthesized at room temperature. The proposed microcantilever system is a sandwich structure composed of chromium (Cr) electrodes and a sputtered AlN film. The key issue for cantilever fabrication is the growth at room temperature of the AlN layer by reactive sputtering, making possible the innovative compatibility of piezoelectric MEMS devices with CMOS circuits already processed. AlN and Cr have been etched by inductively coupled plasma (ICP) dry etching using a BCl3–Cl2–Ar plasma chemistry. As part of the novelty of the post-CMOS micromachining process presented here, a silicon Si (1 0 0) wafer has been used as substrate as well as the sacrificial layer used to release the microcantilevers. In order to achieve this, the Si surface underneath the structure has been wet etched using an HNA (hydrofluoric acid + nitric acid + acetic acid) based solution. X-ray diffraction (XRD) characterization indicated the high crystalline quality of the AlN film. An atomic force microscope (AFM) has been used to determine the Cr electrode surface roughness. The morphology of the fabricated devices has been studied by scanning electron microscope (SEM). The cantilevers have been piezoelectrically actuated and their out-of-plane vibration modes were detected by vibrometry.

Short-term cognitive-behavioural group treatment for hoarding disorder: a naturalistic treatment outcome study

The study aim was to test whether a 12-week publically rebated group programme, based upon Steketee and Frost's Cognitive Behavioural Therapy-based hoarding treatment, would be efficacious in a community-based setting. Over a 3-year period, 77 participants with clinically significant hoarding were recruited into 12 group programmes. All completed treatment; however, as this was a community-based naturalistic study, only 41 completed the post-treatment assessment. Treatment included psychoeducation about hoarding, skills training for organization and decision making, direct in-session exposure to sorting and discarding, and cognitive and behavioural techniques to support out-of-session sorting and discarding, and nonacquiring. Self-report measures used to assess treatment effect were the Savings Inventory-Revised (SI-R), Savings Cognition Inventory, and the Depression, Anxiety and Stress Scales. Pre-post analyses indicated that after 12 weeks of treatment, hoarding symptoms as measured on the SI-R had reduced significantly, with large effect sizes reported in total and across all subscales. Moderate effect sizes were also reported for hoarding-related beliefs (emotional attachment and responsibility) and depressive symptoms. Of the 41 participants who completed post-treatment questionnaires, 14 (34%) were conservatively calculated to have clinically significant change, which is considerable given the brevity of the programme judged against the typical length of the disorder. The main limitation of the study was the moderate assessment completion rate, given its naturalistic setting. This study demonstrated that a 12-week group treatment for hoarding disorders was effective in reducing hoarding and depressive symptoms in an Australian clinical cohort and provides evidence for use of this treatment approach in a community setting. Copyright © 2016 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: A 12-week group programme delivered in a community setting was effective for helping with hoarding symptoms with a large effect size. Hoarding beliefs (emotional attachment and responsibility) and depression were reduced, with moderate effect sizes. A third of all participants who completed post-treatment questionnaires experienced clinically significant change. Suggests that hoarding CBT treatment can be effectively translated into real-world settings and into a brief 12-session format, albeit the study had a moderate assessment completion rate.

Effects of affective and anxiety disorders on outcome in problem gamblers attending routine cognitive-behavioural treatment in South Australia

This study evaluated the influence of 12-month affective and anxiety disorders on treatment outcomes for adult problem gamblers in routine cognitive–behavioural therapy. A cohort study at a state-wide gambling therapy service in South Australia. Primary outcome measure was rated by participants using victorian gambling screen (VGS) ‘harm to self’ sub-scale with validated cut score 21? (score range 0–60) indicative of problem gambling behaviour. Secondary outcome measure was Work and Social Adjustment Scale (WSAS). Independent variable was severity of affective and anxiety disorders based on Kessler 10 scale. We used propensity score adjusted random-effects models to estimate treatment outcomes for sub-populations of individuals from baseline to 12 month follow-up. Between July, 2010 and December, 2012, 380 participants were eligible for inclusion in the final analysis. Mean age was 44.1 (SD = 13.6) years and 211 (56 %) were males. At baseline, 353 (92.9 %) were diagnosed with a gambling disorder using VGS. For exposure, 175 (46 %) had a very high probability of a 12-month affective or anxiety disorder, 103 (27 %) in the high range and 102 (27 %) in the low to moderate range. For the main analysis, individuals experienced similar clinically significant reductions (improvement) in gambling related outcomes across time (p\0.001). Individuals with co-varying patterns of problem gambling and 12 month affective and anxiety disorders who present to a gambling help service for treatment in metropolitan South Australia

PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate

BACKGROUND: Loss of the tumor suppressor phosphatase and tensin homolog (PTEN) occurs frequently in prostate cancers. Preclinical evidence suggests that activation of PI3K/AKT signaling through loss of PTEN can result in resistance to hormonal treatment in prostate cancer. OBJECTIVE: To explore the antitumor activity of abiraterone acetate (abiraterone) in castration-resistant prostate cancer (CRPC) patients with and without loss of PTEN protein expression. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively identified patients who had received abiraterone and had hormone-sensitive prostate cancer (HSPC) and/or CRPC tissue available for PTEN immunohistochemical analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was overall survival from initiation of abiraterone treatment. Relationship with outcome was analyzed using multivariate Cox regression and log-rank analyses. RESULTS AND LIMITATIONS: A total of 144 patients were identified who had received abiraterone post-docetaxel and had available tumor tissue. Overall, loss of PTEN expression was observed in 40% of patients. Matched HSPC and CRPC tumor biopsies were available for 41 patients. PTEN status in CRPC correlated with HSPC in 86% of cases. Loss of PTEN expression was associated with shorter median overall survival (14 vs 21 mo; hazard ratio [HR]: 1.75; 95% confidence interval [CI], 1.19-2.55; p=0.004) and shorter median duration of abiraterone treatment (24 vs 28 wk; HR: 1.6; 95% CI, 1.12-2.28; p=0.009). PTEN protein loss, high lactate dehydrogenase, and the presence of visceral metastases were identified as independent prognostic factors in multivariate analysis. CONCLUSIONS: Our results indicate that loss of PTEN expression was associated with worse survival and shorter time on abiraterone treatment. Further studies in larger and prospective cohorts are warranted. PATIENT SUMMARY: PTEN is a protein often lost in prostate cancer cells. In this study we evaluated if prostate cancers that lack this protein respond differently to treatment with abiraterone acetate. We demonstrated that the survival of patients with loss of PTEN is shorter than patients with normal PTEN expression.

Guided imagery to improve functional outcomes post-anterior cruciate ligament repair: randomized-controlled pilot trial

Imagery can improve functional outcomes post-anterior cruciate ligament repair (ACLR). Research is needed to investigate potential mechanisms for this effect. The aim of this study was to (a) evaluate the effectiveness of an imagery intervention to improve functional outcomes post-ACLR, and (b) explore potential mechanisms. A randomized-controlled pilot trial was conducted. Participants were randomized to guided imagery and standard rehabilitation or standard rehabilitation alone (control). The primary outcome was knee strength 6-month post-operatively. Secondary outcomes were knee laxity at 6-months, and change in psychological (self-efficacy) and neurohormonal (adrenaline, noradrenaline, dopamine) variables. Participants (n=21; 62% male) were 34.86 (SD 8.84) years. Following the intervention, no statistical differences between groups for knee strength extension at 180°/s (t=-0.43, P=0.67), or at 60°/s (t=-0.72, P=0.48) were found. A statistically significant effect was found for knee laxity, F=4.67, P<0.05, mean difference of -3.02 (95% CI -4.44 to -1.60), favoring the intervention. No differences were found for self-efficacy; however, an overall effect was found for noradrenaline, F(1, 19) 19.65, P<0.001, η(2) =0.52, and dopamine, F(1, 19) 6.23, P=0.02, η(2) =0.29, favoring the intervention. This imagery intervention improved knee laxity and healing-related neurobiological factors.

Inter-professional clinical handover in post-anaesthetic care units: tools to improve quality and safety

OBJECTIVES: To examine quality and safety in inter-professional clinical handovers in Post Anaesthetic Care Units (PACUs) and make recommendations for tools to standardize handover processes.
DESIGN: Mixed methods combining data from observations and focus groups.
SETTING: Three PACUs, one public tertiary hospital and two private hospitals.
PARTICIPANTS: Observations were made of 185 patient handovers from anaesthetists to nurses. Eight focus groups were conducted with 62 staff (15 anaesthetists and 47 nurses) across the study sites.
INTERVENTION: Inter-professional clinical handovers in PACU's.
MAIN OUTCOME MEASURES: Characteristics of the structure and processes that support safe inter-professional PACU handover practice.
RESULTS: Characteristics of the process, content, activities and risks during anaesthetist to nurse patient handover into the PACU were integrated into four steps in the PACU handover process summarized by the acronym COLD (Connect, Observe, Listen and Delegate), a verbal communication tool (ISoBAR), a checklist of critical information for safe patient transfer into PACU and a matrix of factors perceived to increase handover risk.
CONCLUSIONS: The standard structure and checklists for optimal content of patient handovers were derived from existing practices and consensus, hence, expected to provide ecologically valid and practical resources to improve quality and safety during clinical handovers in the PACU.

Medical burden, body mass index and the outcome of psychosocial interventions for bipolar depression

Objective: Individuals with bipolar disorder experience a disproportionately high incidence of medical co-morbidity and obesity. These health-related problems are a barrier to recovery from mood episodes and have been linked with unfavorable responses to pharmacological treatment. However, little is known about whether and how these characteristics affect responses to adjunctive psychotherapy. Method: Embedded in the Systematic Treatment Enhancement Program for Bipolar Disorder was a randomized controlled trial of psychotherapy for bipolar depression comparing the efficacy of intensive psychotherapy plus pharmacotherapy with collaborative care (a three-session psycho-educational intervention) plus pharmacotherapy. We conducted a post-hoc analysis to evaluate whether medical burden and body mass index predicted and/or moderated the likelihood of recovery and time until recovery from a depressive episode among patients in the two treatments. Results: Participants who had medical co-morbidity and body mass index data constituted 199 of the 293 patients in the original Systematic Treatment Enhancement Program for Bipolar Disorder trial. Higher medical burden predicted a lower likelihood of recovery from depression in both treatment conditions (odds ratio = 0.89), but did not moderate responses to intensive psychotherapy vs collaborative care. Intensive psychotherapy yielded superior recovery rates for individuals of normal body mass index (odds ratio= 2.39) compared with collaborative care, but not among individuals who were overweight or obese. Conclusion: Medical co-morbidity and body weight impacts symptom improvement and attention to this co-morbidity may inform the development of more personalized treatments for bipolar disorder.